Abnormal response of luteinizing hormone beta subunit to thyrotrophin‐releasing hormone in patients with non‐functioning pituitary adenoma

Abstract

It has been suggested that the response of free beta-subunit of LH (LH beta) to TRH is the most useful in-vivo marker of gonadotroph adenomas in patients with non-functioning pituitary adenomas (NFPA). The aim of the present study was to investigate LH beta secretion in patients with NFPA in whom other markers of gonadotroph adenomas, such as supranormal basal concentrations or responses of intact gonadotrophins to TRH, were absent. Serum basal levels of LH beta LH and FSH were evaluated in 80 patients with NFPA showing normal levels of intact gonadotrophin, 20 with PRL-secreting adenomas, 25 with GH-secreting adenomas and 58 healthy subjects. Moreover, LH beta, LH, FSH and alpha-subunit (alpha-SU) were evaluated in 27 patients with NFPA in whom intact gonadotrophin responses to TRH were absent, 8 with PRL-oma, 7 with GH-oma and 17 healthy subjects before and 20, 30 and 60 minutes after the intravenous administration of either 200 micrograms TRH or placebo. A response was considered present when serum LH beta increased by at least 50% above basal levels. LH beta was evaluated using a new assay based on the sequestration of the combined and free alpha-SU by an anti alpha-SU biotinylated monoclonal antibody (MAb) and the subsequent measurement of the LH beta by an IFMA method employing two MAbs directed towards two different epitopes on LH beta. Intact LH and FSH were assayed with an IFMA method and alpha-SU with an IRMA method. In basal conditions, no significant difference in the mean values of LH beta was observed among patients with different types of tumour and normal controls. In 9 of 27 (33%) patients with NFPA, TRH caused an abnormal elevation of serum LH beta (net increase 410 +/- 403%, range 71-1300) which was completely dissociated from changes in intact gonadotrophins. Of the 5 patients who had a TRH test repeated after transsphenoidal surgery, abnormal LH beta responses disappeared in 2 and were maintained in 3. Disappearance of LH beta response occurred only in patients in whom improvement of visual field and radiological imaging after adenomectomy was observed. In contrast, in all patients with pituitary tumours other than NFPA and healthy subjects a response to TRH was absent (net increase ranging from 0 to 23%). Immunofluorescence, performed on 14 NFPA removed from patients either responsive or unresponsive to TRH, showed a variable proportion of cells positive for LH beta, without a significant difference between the two groups. These results indicate that measurement of basal LH beta is of poor value in the diagnosis of non-functioning pituitary adenomas and the identification of gonadotroph adenomas among non-functioning pituitary adenomas. Conversely, an abnormal response of free LH beta to TRH occurs in about a third of patients with low/normal basal gonadotrophins unresponsive to TRH stimulation.